• Archives of Pharmacal Research
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• v.22 no.2
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• pp.113-118
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• 1999

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic $5-HT_{2}$ receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompeti-tive (MI-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsyaptic $5-HT_{2}$receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin $5-HT_{2}$receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the poststynaptic $5-HT_{2}$ receptors.

• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.421-426
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• 1997

We evaluated the in vivo kinetics, distribution, and pharmacology of N-(4-[$^{18}F$]fluoromethylbenzyl)spiperone ([$^{18}F$]FMBS), a newly developed derivative of spiperone, as a potentially more selective radiotracer for the dopamine (DA) $D_2$ receptors. Mice received 1.9-3.7 MBq (1.8-3.6 nmol/kg) of [$^{18}F$]FMBS by tail vein injection. The time course and regional distribution of the tracer in brain were assessed. Blocking studies were carried out by intravenously preinjecting DA $D_2$ receptor blockers (spiperone, butaclamol) as well as drugs with high affinity for DA $D_1$ (SCH 23390), DA transporter (GBR 12909), and serotonin $S_2$ ($5-HT_2$) (ketanserin) sites. After injection of the tracer, the radioactivity in striatum increased steadily over time, resulting in a striatal-to-cerebellar ratio of 4.8 at 120 min postinjection. By contrast, the radioactivity in cerebellum, frontal cortex, and remaining cortex washed out rapidly. Preinjection of unlabeled FMBS (1 mg/kg) and spiperone (1 mg/kg) reduced [$^{18}F$]FMBS striatal-to-cerebellar ratio by 41% and 80%, respectively. (+)-Butaclamol (1 mg/kg) blocked 80% of the striatal [$^{18}F$]FMBS binding, while (-)-butaclamol (1 mg/kg) did not. Preinjection of SCH 23390 (1 mg/kg) and GBR 12909 (5 mg/kg) had no significant effect on [$^{18}F$]FMBS binding. Ketanserin (1 mg/kg), a ligand for the $5-HT_2$ receptors, did not cause significant inhibition either in striatum, in frontal cortex, or the remaining cortex. The results demonstrate that [$^{18}F$]FMBS labels DA $D_2$ receptors selectively in vivo in the mouse brain. It may hold promise as a selective radiotracer for studying DA $D_2$ receptors in vivo by PET.

• Proceedings of the Zoological Society Korea Conference
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• 1996.10a
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• pp.152.2-152
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• 1996

No Abstract, See Full Text

• Korean Journal of Veterinary Research
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• v.39 no.3
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• pp.463-471
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• 1999

Magnesium($Mg^{2+}$) is one of the most abundant intracellular divalent cation. Although recent studies demonstrate that adrenergic receptor stimulation evokes marked changes in $Mg^{2+}$ homeostasis, the regulation of $Mg^{2+}$ by dopaminergic receptor stimulation is not yet known. In this work, we used dopaminergic agents to identify which type(s) of receptors were involved in the mobilization of $Mg^{2+}$ by dopaminergic receptor stimulation in the perfused rat hearts, isolated myocytes and circulating blood. The $Mg^{2+}$ content was measured by atomic absorbance spectrophotometry. Dopamine(DA), apomorphine(APO) and pergolide stimulated $Mg^{2+}$ efflux in the perfused rat hearts and these effects were inhibited by haloperidol or fluphenazine, nonselective dopaminergic antagonists. SKF38393, a selective doparminergic agonist, increased $Mg^{2+}$ efflux from the perfused hearts in dose dependant manners and SKF38393-induced $Mg^{2+}$ efflux was blocked by haloperidol. However, dopaminergic agonists-induced $Mg^{2+}$ efflux was potentiated in the presence of sulpiride or eticlopride, $D_2$-selective antagonist, from the perfused hearts. This increase of $Mg^{2+}$ efflux was blocked by haloperidol or imipramine. DA or pergolide increased in circulating $Mg^{2+}$ from blood. By contrast, PPHT stimulated $Mg^{2+}$ influx(a decrease in efflux) from the perfused hearts and circulating blood. PPHT-induced $Mg^{2+}$ influx was blocked by fluphenazine in the perfused hearts. DA-stimulated $Mg^{2+}$ efflux was inhibited by dopaminergic antagoinst in the isolated myocytes. In conclusion, the flux of $Mg^{2+}$ is modulated by DA receptor activation in the rat hearts. The efflux of $Mg^{2+}$ can be increased by $D_1$-receptor stimulation and decreased by $D_2$-receptor stimulation, respectively.

• 대한핵의학회:학술대회논문집
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• 2005.11a
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• pp.317.1-317.1
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• 2005

• Proceedings of the Zoological Society Korea Conference
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• 2001.10a
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• pp.177.1-177
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• 2001

No Abstract, See Full Text

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.219-224
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• 2012

Understanding how the b-wave of the electroretinogram (ERG) is generated by full-field light stimulation is still a challenge in visual neuroscience. To understand more about the origin of the b-wave, we studied the contributions of gap junctions to the ERG b-wave. Many types of retinal neurons are connected to similar and different neighboring neurons through gap junctions. The photopic (cone-dominated) ERG, stimulated by a small light beam, was recorded from goldfish (Carassius auratus) using a corneal electrode. Data were obtained before and after intravitreal injection of agents into the eye under a photopic illumination level. Several agents were used to affect gap junctions, such as dopamine D1 and D2 receptor agonists and antagonists, a nitric oxide (NO) donor, a nitric oxide synthase (NOS) inhibitor, the gap junction blocker meclofenamic acid (MFA), and mixtures of these agents. The ERG b-waves, which were enhanced by MFA, sodium nitroprusside (SNP), SKF 38393, and sulpiride, remained following application of a further injection of a mixture with MFA. The ERG b-waves decreased following $N^G$-nitro-L-arginine methyl ester (L-NAME), SCH 23390, and quinpirole administration but were enhanced by further injection of a mixture with MFA. These results indicate that gap junction activity influences b-waves of the ERG related to NO and dopamine actions.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.240-244
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• 1996

The effects of chronic treatment with haloperidol on the binding capacities of dopamine(DA) $D_2$-like receptor were investigated in rat striatum and olfactory tubercle. The authors tried to confirm the dose-response effects with usual dose and low dose haloperidol. Rats were treated with haloperidol(0.05, 0.15, 0.5, 1.5mg/kg/day in drinking water) for four weeks. Saturation analysis of the binding of [$^3H$]spiperone to striatal membranes showed that the haloperidol treatment(0.05, 0.5, 1.5mg/kg) induced significant proliferation. The changes of dissociation constant(Kd) were not significant in striatum. The maximal binding density(Bmax) and Kd increased remarkably following the treatment with usual dose haloperidol (1.5mg/kg) in olfactory tubercle. Although there was increasing trend other the treatment with low dose haloperidol, the change of Bmax was not significant statistically. The present findings indicate that low dose haloperidol induces the proliferation of DA $D_2$-like receptor in striatum and interact with the dopaminergic transmission which might underlie the antipsychotic effect. This finding may support the recent clinical suggestion on the low dose strategy in the treatment of schizophrenia.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.411-416
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• 2023

Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.2
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• pp.287-291
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• 1999

Dopamine agonists are commonly used in the medical treatment of prolactinomas. Bromocriptine has been the most widely used ergot derivative for two decades. Its oral administration, at a daily dose of $2.5{\sim}7.5mg$, restored normal gonadal function and normoprolactinemia in about 80% of patients. Nevertheless, a subset of patients could not achieve normal prolactin levels or resume normal gonadal function despite $15{\sim}30mg$/day bromocriptine for at least 6 months. Subsequently, these prolactinomas were consedered to be resistant to bromocriptine. The percentage of bromocriptine - resistant prolactinoma patients reported in the literature varies between 5 and 17% according to the series. Patients with bromocriptine resistance or bromocriptine intolerance have, however, been treated with other dopamine agonists, such as lysuride, pergolide, cabergoline, or quinagolide. Until cabergoline recently gained a product licence in the UK, there was no alternative dopamine agonist with a licence for this purpose. Quinagolide (CV $205{\sim}502$, Norprolac, Sandoz) is a nonergot dopamine agonist with improved selectivity for the D2 receptor, designed to retain the active pharmacophore of bromocriptine without the ergot moiety that might be responsible for side - effects. We have experienced a case of bromocriptine resistant hyperprolactinemia which was reponsive to pergolide. So we report this case with a brief review of literatures.